This work will be an extension of our previous studies of the effects of undernutrition on brain development: In a series of papers we have demonstrated that in the rat, prenatal undernutrition results in significant decreases in cebrebral parameter (weight, cortical thickness, cell number (DNA) and protein content). Reductions were also found in body weight and placental weight. We have also reported that such deficiencies persist through the second generation (a nonmendelian inheritance). In this project, it is proposed to extend such studies to at least 5 generations of rats that are chronically protein undernourished, both in utero and after birth throughout life. Such an animal colony might be considered a strictly controlled analog of chronically undernourished human populations. In particular it is planned: 1) To monitor the nutritional status of such animals (changes in blood constituents, fertility and mortality rates). 2) To investigate whether brain parameters (cerebral wet and dry weight, cortical thickness, cortical area, neuron packing density, neuron/glia ratio, neuronal perikarion size, dendritic tree (Golgi-Cox), cerebral DNA (cell number) and protein at various developmental milestones, continue to decrease in succeeding generations, or whether they reach plateaus, simultaneously or separately, and if so, after how many generations. 3) To investigate whether such animals or their offspring can be rehabilitated by restoration of protein in the diet, or by administration of growth hormone to pregnant animals (mobilization of maternal nutrient reserves). 4) To apply studies 2-3 specifically to various regions of the brain. BIBLIOGRAPHIC REFERENCES: 1. Zamenhof, S. and van Marthens, E.: Neonatal and Adult Brain Parameters in Mice Selected for Adult Brain Weight. Developmental Psychobiology, 1976, in press. 2. Zamenhof, S., van Marthens, E., and Shimomaye, S.Y.: The Effects of Early Maternal Protein Deprivation on Fetal Development. Federation Proc., 1976, in press.